Effects Of Amphetamine Research Articles

The effects of amphetamine exposure on stress susceptibility in mice

Substance use disorders (SUDs) and their many psychiatric comorbidities, including major depression and anxiety disorders, are characterized by significant sex differences. Although the causes of SUDs and their psychiatric comorbidities remain unknown, stress has been heavily implicated in their etiology. Indeed, one leading hypothesis regarding the basis of clinically observed sex differences in psychopathology argues that differences in stress susceptibility and stress exposure play key roles. Consistent with this, differences in stress susceptibility and reactivity in females compared to males have been documented across multiple species. A wide range of environmental, genetic, and epigenetic factors are also thought to impact stress susceptibility, but whether there are sex differences in the effects of specific susceptibility factors remains understudied. Preclinical work suggests that a history of cocaine exposure can increase susceptibility to stress in males, but whether similar effects occur in females following stimulant exposure has not been established. The current work examined the impact of repeated amphetamine administration on subsequent susceptibility to mild sub-chronic stress in male and female mice. In addition to examining behavior, potential sex differences in the effects of stress and amphetamine on the expression of several genes were evaluated. Our results reveal several significant sex differences in the behavioral effects of amphetamine and stress in the elevated plus maze, forced swim test, and novelty-suppressed feeding test. However, in contrast to our initial hypothesis, a history of amphetamine did not lead to an overall increase in stress susceptibility across multiple tests in males or females.

Time-on-task-related decrements in performance in the rodent continuous performance test are not caused by physical disengagement from the task.

Attention deficits, a hallmark of many neuropsychiatric disorders, significantly impair quality of life and functional outcome for patients. Continuous Performance Tests (CPTs) are widely used to assess attentional function in clinical settings and have been adapted for mice as the rodent Continuous Performance Test (rCPT). In this study, we combined traditional analyses of rCPT performance with markerless pose estimation using DeepLabCut and visual field analysis (VFA) to objectively measure the orientation of mice toward stimuli during rCPT sessions. Additionally, we extended session lengths to assess performance decrements over time. Our findings show that extending rCPT sessions from 45 to 90 minutes results in a significant decline in performance in male mice, which aligns with performance decrements observed in clinical research. Importantly, physical engagement with the task remained relatively stable throughout the session, even as performance deteriorated. This suggests that the performance decline specifically reflects a time-on-task (TOT)-dependent vigilance decrement rather than physical disengagement. We also investigated the effects of amphetamine, an FDA-approved treatment for attention-deficit/hyperactivity disorder (ADHD), on rCPT performance. Amphetamine significantly improved rCPT performance in male mice by reducing false alarms without modulating orientation or physical engagement with the task stimuli. Collectively, these findings validate a behavioral tracking platform for objectively measuring physical engagement in the rCPT and a task modification that accentuates TOT-dependent performance decrements, enhancing the translational value of the rCPT for studies related to human neuropsychiatric disorders.

Dopamine mediates a directionally opposite correlation between empathy and the reinforcing effects of amphetamine and gambling in people with gambling disorder vs. healthy controls

Understanding the relationship between empathy, subjective effects of addictive reinforcers and dopamine function in people with gambling disorder (PGD) vs. healthy controls (HCs) may inform GD treatment. The current investigation addressed this issue via retrospective analysis of data from three studies using amphetamine and a slot machine (SLOTS) as reinforcers in PGD and HCs. The Empathy scale of Eysenck's Impulsiveness Questionnaire assessed trait Empathy. The Gamblers Beliefs Questionnaire assessed cognitive distortions. The Eysenck Lie scale assessed socially desirable responding. PET scans quantified dopamine receptor expression and amphetamine-induced dopamine release in Study 1. Pre-treatment with the D2-receptor (D2R)-preferring antagonist, haloperidol or D1R-D2R antagonist, fluphenazine before SLOTS tested the role of D2 autoreceptors and post-synaptic D2R in Study 2. Pre-treatment with the multi-system indirect dopamine agonist, modafinil before SLOTS assessed the reliability of correlations in PGD. Striatal D2R expression predicted greater Empathy and lower amphetamine ‘Liking’ in HCs, and predicted greater symptom severity in PGD. Empathy predicted lower ‘Exciting’ effects of SLOTS under placebo in HCs; no correlation emerged under either antagonist. Relative to placebo, haloperidol decreased, whereas fluphenazine increased, the positive correlation between Empathy and Exciting effects of SLOTS in PGD. Modafinil markedly reduced the positive correlation between Empathy and Exciting effects of SLOTS seen under placebo in PGD. Empathy predicted greater cognitive distortions in PGD in all studies. Lie scale variance influenced several primary effects. Prior research linking the insula with Empathy, reactivity to interoceptive signals for risky rewards (uncertainty), and cognitive distortions, provides a parsimonious account for these results.

Locomotion changes in methamphetamine and amphetamine withdrawal: a systematic review.

Despite extensive preclinical research over the years, a significant gap remains in our understanding of the specific effects of methamphetamine (METH) and amphetamine (AMPH) withdrawal. Understanding these differences could be pivotal to unveiling the unique pathophysiology underlying each stimulant. This may facilitate the development of targeted and effective treatment strategies tailored to the specific characteristics of each substance. Following PRISMA guidelines, this systematic review was conducted to examine alterations in spontaneous locomotor activity, specifically horizontal activity, in animals experiencing withdrawal from extended and repeated administration of AMPH or METH. Original articles were retrieved from four electronic databases, supplemented by a review of the references cited in the published papers. A total of thirty-one full-length articles (n = 31) were incorporated in the analysis. The results indicated that six studies documented a significant increase in horizontal activity among animals, seven studies reported decreased locomotion, and eighteen studies (8 AMPH; 10 METH) reported no significant alterations in the animals' locomotor activity. Studies reporting heightened locomotion mainly employed mice undergoing withdrawal from METH, studies reporting diminished locomotion predominantly involved rats undergoing withdrawal from AMPH, and studies reporting no significant changes in horizontal activity employed both rats and mice (12 rats; 6 mice). Drug characteristics, routes of administration, animal models, dosage regimens, duration, and assessment timing seem to influence the observed outcomes. Despite more than 50% of papers enlisted in this review indicate no significant changes in the locomotion during the stimulant withdrawal, the unique reactions of animals to withdrawal from METH and AMPH reported by some underscore the need for a more nuanced understanding of stimulant withdrawal.

Neural effects of dopaminergic compounds revealed by multi-site electrophysiology and interpretable machine-learning.

Neuropsychopharmacological compounds may exert complex brain-wide effects due to an anatomically and genetically broad expression of their molecular targets and indirect effects via interconnected brain circuits. Electrophysiological measurements in multiple brain regions using electroencephalography (EEG) or local field potential (LFP) depth-electrodes may record fingerprints of such pharmacologically-induced changes in local activity and interregional connectivity (pEEG/pLFP). However, in order to reveal such patterns comprehensively and potentially derive mechanisms of therapeutic pharmacological effects, both activity and connectivity have to be estimated for many brain regions. This entails the problem that hundreds of electrophysiological parameters are derived from a typically small number of subjects, making frequentist statistics ill-suited for their analysis. We here present an optimized interpretable machine-learning (ML) approach which relies on predictive power in individual recording sequences to extract and quantify the robustness of compound-induced neural changes from multi-site recordings using Shapley additive explanations (SHAP) values. To evaluate this approach, we recorded LFPs in mediodorsal thalamus (MD), prefrontal cortex (PFC), dorsal hippocampus (CA1 and CA3), and ventral hippocampus (vHC) of mice after application of amphetamine or of the dopaminergic antagonists clozapine, raclopride, or SCH23390, for which effects on directed neural communication between those brain structures were so far unknown. Our approach identified complex patterns of neurophysiological changes induced by each of these compounds, which were reproducible across time intervals, doses (where tested), and ML algorithms. We found, for example, that the action of clozapine in the analysed cortico-thalamo-hippocampal network entails a larger share of D1-as opposed to D2-receptor induced effects, and that the D2-antagonist raclopride reconfigures connectivity in the delta-frequency band. Furthermore, the effects of amphetamine and clozapine were surprisingly similar in terms of decreasing thalamic input to PFC and vHC, and vHC activity, whereas an increase of dorsal-hippocampal communication and of thalamic activity distinguished amphetamine from all tested anti-dopaminergic drugs. Our study suggests that communication from the dorsal hippocampus scales proportionally with dopamine receptor activation and demonstrates, more generally, the high complexity of neuropharmacological effects on the circuit level. We envision that the presented approach can aid in the standardization and improved data extraction in pEEG/pLFP-studies.

Augmentation of intracranial self-stimulation induced by amphetamine-like drugs in Period circadian regulator 2 knockout mice is associated with intracellular Ca2+ levels

Over the past decade, new psychoactive substances (NPS) have emerged in the illegal drug market and have continued to attract attention from the international community. Among these, amphetamine-like NPS, classified as stimulants, constitute a significant proportion. However, the pharmacological characteristics and mechanisms underlying addiction to amphetamine-like NPS remain poorly understood. Given that circadian rhythms are linked to the brain stimulation effects of methamphetamine (METH) and amphetamine, we investigated the effects of METH, 1-(4-methoxyphenyl)-N-methylpropan-2-amine (PMMA), and 1-(benzofuran-5-yl)-N-ethylpropan-2-amine (5-EAPB) on intracranial self-stimulation (ICSS) in wild-type (WT) or Period circadian regulator 2 knockout mice. Amphetamine-like drugs increase intracellular Ca2+ levels to provoke dopamine release, so we examined the impact of Per2 knockdown on intracellular Ca2+ levels in PC12 cells to elucidate a potential mechanism underlying NPS-induced ICSS enhancement. Our ICSS results showed that METH and PMMA significantly increased brain stimulation in Per2 knockout mice compared to WT mice. Similarly, METH and PMMA induced higher Ca2+ fluorescence intensity in Per2 knockdown PC12 cells than in control cells. In contrast, 5-EAPB did not produce significant changes in either ICSS or Ca2+ signaling. These findings suggest that Per2 plays a crucial role in the brain stimulation effects of amphetamine-like drugs through the regulation of intracellular Ca2+.

Adicciones y enfermedades neurodegenerativas: Dianas comunes en la búsqueda de nuevas terapias

Pleiotrophin (PTN) is a neurotrophic factor for dopaminergic neurons whose levels of expression are increased in the brain of alcoholic patients, in rodents after the administration of amphetamine and in patients with different neurodegenerative diseases. PTN limits the neurotoxic effects of amphetamines in the nigrostriatal pathway which, in humans, can lead to Parkinson’s disease. Additionally, PTN limits the rewarding effects of alcohol. PTN is an endogenous inhibitor of the Receptor Protein Tyrosine Phosphatase Z1 (PTPRZ1, also known as RPTPβ/ζ or Phosphacan). We have shown that the effects of PTN can be reproduced with selective inhibitors of RPTPβ/ζ that we obtained through a rational drug design program. The leading RPTPβ/ζ inhibitory compound, MY10, significantly reduces alcohol consumption in animal models and regulates the neuroimmune response to this drug, blocking as a result the decrease in hippocampal neurogenesis produced by alcohol, revealing important differences between sexes. RPTPβ/ζ has been shown to be a key anchor for cell surface perineuronal nets (PNNs), which play an important role in alcohol addiction. In the hippocampus PNNs play a fundamental role in neurogenesis and learning, suggesting that the effects of MY10 on alcohol consumption and the decrease in hippocampal neurogenesis induced by this drug could be mediated by the actions of RPTPβ/ζ inhibition on the PNNs. Keywords: Alcohol; amphetamine; pleiotrophin; neuroinflammation; addiction; neurodegeneration

Forebrain EAAT3 Overexpression Increases Susceptibility to Amphetamine-Induced Repetitive Behaviors.

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder characterized by intrusive obsessive thoughts and compulsive behaviors. Multiple studies have shown the association of polymorphisms in the SLC1A1 gene with OCD. The most common of these OCD-associated polymorphisms increases the expression of the encoded protein, excitatory amino acid transporter 3 (EAAT3), a neuronal glutamate transporter. Previous work has shown that increased EAAT3 expression results in OCD-relevant behavioral phenotypes in rodent models. In this study, we created a novel mouse model with targeted, reversible overexpression of Slc1a1 in forebrain neurons. The mice do not have a baseline difference in repetitive behavior but show increased hyperlocomotion following a low dose of amphetamine (3 mg/kg) and increased stereotypy following a high dose of amphetamine (8 mg/kg). We next characterized the effect of amphetamine on striatal cFos response and found that amphetamine increased cFos throughout the striatum in both control and Slc1a1-overexpressing (OE) mice, but Slc1a1-OE mice had increased cFos expression in the ventral striatum relative to controls. We used an unbiased machine classifier to robustly characterize the behavioral response to different doses of amphetamine and found a unique response to amphetamine in Slc1a1-OE mice, relative to controls. Lastly, we found that the differences in striatal cFos expression in Slc1a1-OE mice were driven by cFos expression specifically in D1 neurons, as Slc1a1-OE mice had increased cFos in D1 ventral medial striatal neurons, implicating this region in the exaggerated behavioral response to amphetamine in Slc1a1-OE mice.

Evaluation of the Psychiatric Disorders among Amphetamine Addicts in Rehabilitation Centers: A Cross-Sectional Analysis.

People who are addicted to amphetamines have a much greater chance of developing psychosis compared to those who are not. It is essential to study the behavioral and psychological effects of amphetamines. Therefore, this research aimed to examine conditions such as depression, anxiety, mood, cognitive abilities at the workplace, and social responsibilities by using sociodemographic factors as useful tools in determining effective strategies for preventing, managing, and treating amphetamine addiction. A cross-sectional study among addicts hospitalized at two rehabilitation centers across Saudi Arabia between May and October 2023. A validated questionnaire consisting of psychiatric disorders assessment tools was distributed to healthcare professionals to start an interview with addicts to assess the abnormalities. The results were compared with healthy people (control). The assessment tools used are Hamilton Anxiety and Depression Rating Scale, Young Mania Rating Scale, and Work and Social Adjustment Scale. The data were analyzed using SPSS version 22.0. Pearson correlation coefficients (r) were employed. A total of 60 subjects participated in this study. The participants were divided into two groups (n = 60): group I was control (n = 25) healthy volunteers and group II was amphetamine abusers (n = 35), who were hospitalized for detoxification. The ages ranged from 18 to 60 years old with mean ages of 38.68 (±8.14) and 37.77 (±10.95) years in the control and amphetamine groups, respectively. Among the addicts, the mean severity dependence scale value was 10.46 (±1.82), which denotes high dependency on the illicit drug. The prevalence of high levels of anxiety, depression, and bipolar disorder was significantly higher among addicts when they were compared to healthy people (control). The assessment of the Work and Social Adjustment Scale (WSAS) reflected a higher impairment that minimized their ability to perform the work requirements, home management, social leisure, and relationships. The addiction to amphetamines was associated with high impairment of work performance and social obligations and a negative impact on the addict's mental health. The risk of suffering anxiety, depression, and bipolar is higher than in nonaddict people. These effects are attributed to brain damage, neurotoxicity, and neuronal inflammation, particularly when these substances are abused over extended periods and at higher doses.

Protective effects of amphetamine and methylphenidate against dopaminergic neurotoxicants in SH-SY5Y cells

Full treatment of the second most common neurodegenerative disorder, Parkinson’s disease (PD), is still considered an unmet need. As the psychostimulants, amphetamine (AMPH) and methylphenidate (MPH), were shown to be neuroprotective against stroke and other neuronal injury diseases, this study aimed to evaluate their neuroprotective potential against two dopaminergic neurotoxicants, 6-hydroxydopamine (6-OHDA) and paraquat (PQ), in differentiated human dopaminergic SH-SY5Y cells.Neither cytotoxicity nor mitochondrial membrane potential changes were seen following a 24-hour exposure to either therapeutic concentration of AMPH or MPH (0.001–10 μM). On the other hand, a 24-hour exposure to 6-OHDA (31.25–500 μM) or PQ (100–5000 μM) induced concentration-dependent mitochondrial dysfunction, assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, and lysosomal damage, evaluated by the neutral red uptake assay. The lethal concentrations 25 and 50 retrieved from the concentration-toxicity curves in the MTT assay were 99.9 µM and 133.6 µM for 6-OHDA, or 422 µM and 585.8 µM for PQ. Both toxicants caused mitochondrial membrane potential depolarization, but only 6-OHDA increased reactive oxygen species (ROS). Most importantly, PQ-induced toxicity was partially prevented by 1 μM of AMPH or MPH. Nonetheless, neither AMPH nor MPH could prevent 6-OHDA toxicity in this experimental model.According to these findings, AMPH and MPH may provide some neuroprotection against PQ-induced neurotoxicity, but further investigation is required to determine the exact mechanism underlying this protection.

The role of sex and drug use during adolescence in determining the risk for adverse consequences of amphetamines.

Use of amphetamines during adolescence, a critical period of brain development and reorganization, may lead to particularly adverse outcomes that are long-lasting. Similarly, female users may be uniquely vulnerable to certain aspects of drug use. A recognition of the role of use during adolescence and sex on outcomes of amphetamine and methamphetamine exposure are of critical importance in understanding and treating substance use disorders. This chapter highlights what human research, which has been largely epidemiological, suggests about sex and age differences in drug use patterns and outcomes. We also discuss work in laboratory animals that has typically utilized rats or mice exposed to drugs in a non-contingent manner (i.e., involuntarily) or through volitional self-administration. Lastly, we draw attention to the fact that advancing our understanding of the effects of amphetamine and methamphetamine use, the development of problematic drug taking, and the mechanisms that contribute to relapse will require an emphasis on inclusion of age and sex as moderating factors in future studies.

Contractile Effects of Amphetamine, Pseudoephedrine, Nor-pseudoephedrine (Cathine), and Cathinone on Atrial Preparations of Mice and Humans.

Amphetamine derivatives are used worldwide legally or illegally and intoxications may be accompanied by cardiac arrhythmias. Here, we tested contractile effects of cumulative applied (±)-amphetamine, pseudoephedrine, nor-pseudoephedrine (cathine), and cathinone in electrically stimulated (1 Hz) human right atrial preparations (HAP) and mouse left atrial preparations and in spontaneously beating mouse right atrial preparations. In mouse atrial preparations, amphetamine increased force of contraction and beating rate in a concentration- and time-dependent manner, starting at 1 µM in left atrial preparations to 157.1% ± 3.0% and right atrial preparations to 146.6% ± 9.8% at 10 µM, respectively [mean ± standard error of the mean (SEM); n = 5; P < 0.05]. Pseudoephedrine, cathine, or cathinone alone were ineffective in mouse atrial preparations but after pre-incubation with the phosphodiesterase IV inhibitor rolipram (0.1 µM), a positive inotropic effect was noted (mean ± SEM: pseudoephedrine: 112.3% ± 9.8%; cathine: 109.0% ± 4.3%; cathinone: 138.3% ± 21.2%). The effects of all drugs were greatly attenuated by 10 µM cocaine or 10 µM propranolol treatments. However, In HAP, not only amphetamine (to a mean ± SEM of 208% ± 32%) but also pseudoephedrine (to a mean ± SEM of 287% ± 60%), cathine (to a mean ± SEM of 234% ± 52%), and cathinone (to a mean ± SEM of 217% ± 65%) increased force of contraction without the need of phosphodiesterase inhibition. The contractile effects in HAP were attenuated by 10 µM cocaine and antagonized by 10 µM propranolol. We conclude that amphetamine, pseudoephedrine, cathine, and cathinone act probably via release of noradrenaline from cardiac stores as indirect sympathomimetic agents in mouse and more pronounced in human atrial preparations.

Effects of naltrexone on amphetamine choice in rhesus monkeys and rats.

Clinical amphetamine use is constrained by high abuse potential, and amphetamine use disorder is a persistent clinical problem with no approved medications for its treatment. The opioid antagonist naltrexone has been reported to reduce some abuse-related effects of amphetamine. This study used an amphetamine-versus-food choice procedure in rhesus monkeys and rats to test the hypothesis that naltrexone might serve as either (a) a maintenance medication for amphetamine use disorder treatment or (b) an "abuse-deterrent" adjunct to clinical amphetamine formulations. Male rhesus monkeys and male and female rats were trained to choose between increasing unit doses of intravenous amphetamine and an alternative food reinforcer during daily behavioral sessions. Experiment 1 evaluated effectiveness of continuous naltrexone maintenance to reduce amphetamine-versus-food choice in both monkeys and rats. Experiment 2 combined naltrexone with amphetamine in fixed-proportion amphetamine + naltrexone mixtures to evaluate the effectiveness of naltrexone in both species to reduce mixture choice relative to amphetamine-alone choice. Amphetamine maintained a dose-dependent increase in amphetamine choice in both monkeys and rats. Naltrexone maintenance did not significantly decrease amphetamine choice in either species. Addition of naltrexone to amphetamine reduced amphetamine choices per session in monkeys, but behavior was not reallocated to food choice, and in rats, the addition of naltrexone only decreased food choice without significantly affecting amphetamine choice. These results argue against the use of naltrexone as either (a) a maintenance medication for treatment of amphetamine use disorder or (b) an "abuse-deterrent" adjunct to amphetamine for clinical applications. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Safety comparisons among monoamine oxidase inhibitors against Parkinson’s disease using FDA adverse event reporting system

Monoamine oxidase B (MAO-B) inhibitors are used to control Parkinson’s disease (PD). Selegiline, rasagiline, and safinamide are widely used as MAO-B inhibitors worldwide. Although these drugs inhibit MAO-B, there are pharmacological and chemical differences, such as the inhibitory activity, the non-dopaminergic properties in safinamide, and the amphetamine-like structure in selegiline. MAO-B inhibitors may differ in adverse events (AEs). However, differences in actual practical clinics are not fully investigated. A retrospective study was conducted using FAERS, the largest database of spontaneous adverse events. AE signals for MAO-B inhibitors, including selegiline, rasagiline, and safinamide, were detected using the reporting odds ratio method and compared. Hypocomplementemia, hepatic cyst, hepatic function abnormal, liver disorder and cholangitis were detected for selegiline as drug-specific signals. The amphetamine effect was not confirmed for any of the three MAO-B inhibitors. The tyramine reaction was detected as an AE signal only for rasagiline. Moreover, the REM sleep behavior disorder was not detected as an AE signal for safinamide, suggesting that non-dopaminergic effects might be beneficial. Considering the differences in AEs for MAO-B inhibitors will assist with the appropriate PD medication.

Amphetamine-induced dopamine release in rat: Whole-brain spatiotemporal analysis with [11C]raclopride and positron emission tomography.

Whole-brain mapping of drug effects are needed to understand the neural underpinnings of drug-related behaviors. Amphetamine administration is associated with robust increases in striatal dopamine (DA) release. Dopaminergic terminals are, however, present across several associative brain regions, which may contribute to behavioral effects of amphetamine. Yet the assessment of DA release has been restricted to a few brain regions of interest. The present work employed positron emission tomography (PET) with [11C]raclopride to investigate regional and temporal characteristics of amphetamine-induced DA release across twenty sessions in adult female Sprague Dawley rats. Amphetamine was injected intravenously (2 mg/kg) to cause displacement of [11C]raclopride binding from DA D2-like receptors, assessed using temporally sensitive pharmacokinetic PET model (lp-ntPET). We show amphetamine-induced [11C]raclopride displacement in the basal ganglia, and no changes following saline injections. Peak occupancy was highest in nucleus accumbens, followed by caudate-putamen and globus pallidus. Importantly, significant amphetamine-induced displacement was also observed in several extrastriatal regions, and specifically in thalamus, insula, orbitofrontal cortex, and secondary somatosensory area. For these, peak occupancy occurred later and was lower as compared to the striatum. Collectively, these findings demonstrate distinct amphetamine-induced DA responses across the brain, and that [11C]raclopride-PET can be employed to detect such spatiotemporal differences.

Methamphetamine increases force of contraction in isolated human atrial preparations through the release of noradrenaline

We measured the cardiac contractile effects of the sympathomimetic amphetamine-like drug methamphetamine alone and in the presence of cocaine or propranolol in human atrial preparations. For a more comprehensive analysis, we also examined the effects of methamphetamine in preparations from the left and right atria of mice and, for comparison, analyzed the cardiac effects of amphetamine itself. In human atrial preparations, methamphetamine and amphetamine increased the contractile force, the relaxation rate, and the rate of tension development, and shortened the time to maximum tension and the time to relaxation. Likewise, in mice preparations, methamphetamine and amphetamine increased the contractile force in the left atrium and increased the beating rate in the right atrium. The effect in human atrial preparations started at 1 µM, therefore methamphetamine was less effective and potent than isoproterenol in increasing contractile force. These positive inotropic effects of methamphetamine were greatly attenuated by 10 µM cocaine and abolished by 10 µM propranolol. The inotropic effects of methamphetamine in human atrial preparations were associated with, and are believed to be mediated at least in part by, an increase in the phosphorylation state of the inhibitory subunit of troponin. In conclusion, the sympathomimetic central stimulant drug methamphetamine (as well as amphetamine) increased contractile force and protein phosphorylation, presumably through a release of noradrenaline in isolated human atrial preparations. Thus, methamphetamine acts as an indirect sympathomimetic in the human atrium.

Exertional Heat Stroke and Doping: What About Soldiers? A Case Report of Amphetamine Use

Introduction: Exertional heat stroke is a pathology well known to military doctors because it is not uncommon for our soldiers to regularly make intense efforts in difficult training or operational missions. Idiopathic etiology and genetics are by far the most described. We report for the first time a case of exertional heat stroke secondary to amphetamine use in the military environment and here, let’s raise the issue of ethics in the Army. Case Presentation: A young parachutist soldier presented an episode of general convulsions complicating an exertional heat stroke during an 8 km race in battledress and combat boots. After further investigations, laboratory results found amphetamine in the urine. Even if the soldier only allowed branched chain amino acids (BCAAs) supplements, this exertional heat stroke was due to amphetamine use. After a review of the physiopathological effects of amphetamine, we will recall the various means of screening with their limits. Many of our soldiers consume dietary supplements to be able to better endure the constraints to which they are exposed in internship or operations. Conclusions: Doping, willingly or not, is a reality in our Army, even though we still struggle to understand it. Health and command chains must be vigilant to these lines to preserve the health of our military on the one hand and enforce a code of ethics on the other.

Synthetical effect of microplastics and chiral drug amphetamine on a primary food source algae Chlorella pyrenoids.

The biological effects and fate of the chiral illicit drug amphetamine in the presence and absence of microplastics on freshwater algae (Chlorella pyrenoids), including acute toxicity, growth inhibition, photosynthetic pigment content, oxidative stress, lipid peroxidation, and enantioselective fate were assessed. An agglomeration and the shading effects of microplastics in algae suspension were also determined. Microplastics were observed to increase the toxicity of amphetamine to algae and reduce algae cell growth. Exposed Chlorella pyrenoids exhibited a reduced algae cell counts in an agglomeration test, wherein algae cells decreased between 18% and 56% among treatment groups exposed to 5-50mgL-1 of microplastics. The agglomeration test suggested that microplastics might significantly increase the adverse effect on algae. Furthermore, our experiments demonstrated enantioselective degradation of amphetamine in algae, and demonstrated that the S-enantiomer was preferably degraded by algae cells. Adding microplastics to the algae suspension significantly reduced the enantioselectivity, with an EF value of 0.41 compared with amphetamine-alone group (0.34) after 21d exposure. These results demonstrated the first evidence of microplastics acting as a vehicle to enhance amphetamine toxicity to Chlorella pyrenoids, as well as provided new insights into the co-effect of microplastics and organic contaminants on food source.

Dominance status is associated with a variation in cannabinoid receptor 1 expression and amphetamine reward

The rewarding effects of psychostimulants appear to be distinct between dominant and subordinate individuals. In turn, the endocannabinoid system is an important modulator of drug reward in the nucleus accumbens and medial prefrontal cortex, however the connection with social dominance is yet to be established. Male rats were classified as dominant or subordinate on the basis of their spontaneous agonistic interactions and drug reward was assessed by means of conditioned place preference with amphetamine (AMPH). In addition, the expression of CB1R, CB2R, FAAH1, and DAGLa was quantified from accumbal and cortical tissue samples. Our findings demonstrate that dominant rats required a lesser dose of AMPH to acquire a preference for the drug-associated compartment, thereby suggesting a higher sensitivity to the rewarding effects of AMPH. Furthermore, dominants exhibited a lower expression of CB1R in the medial prefrontal cortex and nucleus accumbens. This study illustrates how CBR1 expression could differentiate the behavioral phenotypes associated to social dominance.

Systematic reviews of the acute effects of amphetamine on working memory and other cognitive performances in healthy individuals, with a focus on the potential influence of personality traits.

This research aimed to systematically review the acute effects of amphetamine (AMP), a dopamine-releasing agent, on working memory (WM) and other cognitive performances. The investigation also aimed to review the impact of personality traits on the subjective and objective effects of AMP and possible links between personality traits and effects of AMP. Previous double-blind controlled studies assessing the main effects of AMP on WM and other cognitive performances in healthy volunteers were systematically reviewed. An electronic search was performed in the PUBMED and SCOPUS databases. Narrative reviews of the influence of personality traits on the subjective and objective effects of AMP were included. Nineteen WM studies were included in the current review. Seven studies found effects of AMP on spatial WM, but only one study found the effect of AMP on verbal WM. Thirty-seven independent studies on other aspects of cognitive performance were identified. Twenty-two reported effects of AMP on cognitive functions. Studies also showed that personality traits are associated with the subjective effects of AMP. However, few studies reported the impacts of personality traits on the objective (such as WM) effects of AMP. Overall, findings indicate that AMP has mixed-effects on spatial WM and other cognitive functions, but it lacks effects on verbal WM. Although there are insufficient studies on objective measures, studies also indicated that the subjective effects of AMP administration are linked to between-person variations in personality traits.